Age‐specific response of skeletal muscle extracellular matrix to acute resistance exercise: A pilot study

Abstract

The extracellular matrix (ECM) plays an essential role in the development, growth and repair of skeletal muscles and serves to transmit contractile force. However, its regulation is poorly understood. This study investigates the age-specificity of the effects of acute resistance exercise on ECM gene expression. To this purpose, five young (YM, 23.8 ± 2.2 yrs.) and 5 elderly (EM, 66.8 ± 4.1 yrs.) men performed one session of unilateral leg press and leg extension exercises. Six hours post-exercise, biopsies were taken from the vastus lateralis muscles of both legs. A PCR array was used to profile the expression of 84 ECM-related genes, of which 6 were validated by qPCR. The PCR array found 9 and 4 ECM-associated genes to be selectively altered (>1.5-fold change) in YM or EM only. Four further genes were upregulated in YM but downregulated in EM. Of the 6 genes validated on individual samples MMP9 expression increased in YM (9.7-fold) and decreased (0.2-fold) in EM. MMP15 was downregulated in EM only (0.6-fold). A significant correlation between leg extension 1 RM and changes in COL7A1 expression (ρ = 0.71) suggests a potential influence of fitness levels. In conclusion, acute resistance exercise affects ECM gene expression at least partly in an age-specific manner. The altered expression of genes encoding matrix metalloproteinases (MMP3, MMP9, MMP15) highlights the role of remodelling processes in the response to an acute bout of resistance exercise. Larger studies are required to verify the age-associated differences in gene expression profiles and establish their functional implications.

Skeletal Muscle Extracellular Matrix – What Do We Know About Its Composition, Regulation, and Physiological Roles? A Narrative Review

“…Especially, MMPs seem to play an important role in these processes (de Sousa Neto et al, 2018). This is further supported by findings that suggest a diminished resistance exercise-induced remodeling capacity of ECM structures in aged muscles (Wessner et al, 2019). While the mechanisms are not yet fully understood, these changes are also believed to directly impair muscle function by hindering fiber contractility (Azizi et al, 2017) and lateral force transmission (Sharafi and Blemker, 2011).…”

“…The transient upregulation of tenascin C and other ECM glycoproteins (e.g., fibronectin and hyaluronic acid) is usually referred to as the "transient matrix, " the appearance of which is considered an essential first step for successful muscle repair, as it provides important cues driving muscle stem cell regenerative potential (Calve et al, 2010;Tierney et al, 2016). The release of ECM glycoproteins is reportedly accompanied by increased MMP-9 activity in young, but decreased MMP-9 and MMP-15 activity in old subjects (Wessner et al, 2019). These findings suggest that an acute bout of resistance exercise triggers a catabolic response in young muscle but that this effect may be impaired at older age.…”

Remodeling the Skeletal Muscle Extracellular Matrix in Older Age—Effects of Acute Exercise Stimuli on Gene Expression

“…In addition to collagen biosynthesis regulation, enzymes belonging to the family of matrix metallopeptidases (MMPs) and their antagonists, the tissue inhibitors of matrix metallopeptidases (TIMPs), may influence tissue remodeling by directly degrading various collagen types [ 49 ]. The genes examined in the present study (COL1A1, COL7A1, MMP2, MMP3, MMP9, MMP15, TIMP1) were selected based on their demonstrated importance for intramuscular connective tissue remodeling (COL1A1, MMP2, MMP9, TIMP1) as well as on the basis of our pilot study, in which we compared their exercise-induced expression between young and elderly men [ 44 ]. The main finding of that study was that conventional resistance exercise (CE) led to a significant upregulation of genes encoding both MMPs (MMP3, MMP9) and collagens (COL1A1) in young men, whereas the same genes were either unaltered (COL1A1) or even downregulated (MMP3, MMP9) in senior men.…”

“…COL1A1 is a gene encoding the collagen type I alpha chain, which is a fibril-forming collagen present in all layers of intramuscular connective tissue and the most abundant form of collagen in muscle [ 55 ]. Earlier studies performed by us [ 44 ] and others [ 56 , 57 ] have shown that an acute bout of conventional (i.e., concentric-eccentric) resistance exercise increases either the expression of COL1A1 or collagen protein fractional synthesis rates within 1.0–8.5 h in young muscle. As compared to these results, the current findings indicate that the exercise-induced activation of genes associated with collagen production may differ between young and elderly subjects, as COL1A1 was decreased 0.84-fold (and COL7A1 virtually unaltered) in CE.…”

“…Acute studies in young humans indicate that genes associated with both the synthesis and degradation of intramuscular connective tissue may be activated through (particularly eccentric) resistance exercise [ 41 , 42 , 43 ]. Pilot data acquired by our group, however, suggest that the genetic response to exercise might differ between young and elderly subjects, with the latter showing a reduced expression of genes responsible for the biosynthesis of connective tissue-degrading enzymes [ 44 ]. Others have proposed that fascial tissues would be best stimulated by the performance of rapid, low-amplitude stretch-shortening cycles (i.e., bouncing movements) or myofascial release techniques like foam rolling, which are assumed to benefit tissue rehydration [ 45 ] but these hypotheses are yet to be explicitly tested.…”